阿帕替尼联合替吉奥治疗肝动脉化疗栓塞术后的原发性肝细胞癌的疗效研究

摘要/Abstract

摘要： 目的：探讨阿帕替尼联合替吉奥治疗肝动脉化疗栓塞术后的原发性肝细胞癌（HCC）的疗效及其药代动力学研究。方法：选取2018年8月至2021年5月我院收治的中晚期HCC患者90例作为研究对象，随机分为观察组和对照组，每组各45例。两组患者均行肝动脉化疗栓塞术(TACE)，对照组患者术后行替吉奥药物辅助治疗，观察组患者术后行阿帕替尼联合替吉奥药物辅助治疗。统计两组患者的不良反应发生率，采用RT-PCR实时分析HCC相关指标蛋白的表达，统计两组患者客观缓解率，跟踪记录两组患者的无进展生存期。结果：观察组患者客观缓解率（64.44%）高于对照组（22.22%，P<0.05）。两组患者发烧、腹痛、恶心呕吐、骨髓抑制等不良反应发生率比较差异均无统计学意义（P>0.05）；观察组患者高血压、蛋白尿、手足综合征等不良反应发生率高于对照组（P<0.05）。观察组、对照组患者无进展生存期分别为12.600（95%CI：11.944~13.256）个月、6.500（95%CI：5.770~7.230）个月，观察组患者无进展生存期长于对照组（P<0.05）。观察组患者治疗后3个月时的AFP、ALT、DCP mRNA相对表达水平均低于对照组（P<0.05）。结论：TACE后HCC患者服用阿帕替尼联合替吉奥是一种安全有效的治疗手段。

关键词: TACE, 原发性肝细胞癌, 阿帕替尼, 临床试验, 替吉奥, 生存率

Abstract: Objective：To investigate the efficacy and pharmacokinetics of apatinib combined with tegio in the treatment of primary liver hepatocellular carcinoma (HCC) after transcatheter arterial chemoembolization(TACE). Methods：90 patients with advanced HCC who were admitted in our hospital from August 2018 to May 2021 were selected. All patients were randomized divided into the observation group and the control group，each group 45 cases. TACE was performed on the two groups of patients， the control group was only given tegio adjuvant therapy after operation， and the observation group was given apatinib combined with tegio adjuvant therapy after operation. The incidence of adverse events in the two groups of patients were recorded. RT-PCR was used to analyze the expression of HCC related index proteins. The treatment remission rate of patients were count. The progression-free survival time of the two groups of patients were recorded. Results：The objective response rate of the observation group was 64.44%，which is higher than that of the control group (22.22%， P<0.05). There was no significant difference in the incidence of adverse events such as fever， abdominal pain， nausea and vomiting， and bone marrow suppression between the two groups of patients (P>0.05). The incidence of adverse reactions such as hypertension， proteinuria， and hand foot syndrome in the observation group was higher than that in the control group (P<0.05). The progression free survival time of the observation group and the control group were 12.600 (95%CI： 11.944-13.256) months and 6.500 (95%CI： 5.770-7.230) months， respectively. The progression free survival time of the observation group was longer than the control group (P<0.05). The relative expression levels of AFP， ALT， and DCP mRNA in the observation group were lower than those in the control group at 3 months after treatment (P<0.05). Conclusion：It is a safe and effective treatment for patients with advanced primary liver cancer after TACE to take apatinib in combination with tegio.

Key words: TACE, Primary liver hepatocellular carcinoma, Apatinib, Clinical trial, Tegio, Survival rate

中图分类号:

吴晋周, 靳建旭. 阿帕替尼联合替吉奥治疗肝动脉化疗栓塞术后的原发性肝细胞癌的疗效研究[J]. 中国医药导刊, 2023, 25(9): 952-956.

WU Jinzhou, JIN Jianxu. Efficacy of Apatinib Combined with Tegio in the Treatment of Primary Liver Hepatocellular Carcinoma after Transcatheter Arterial Chemoembolization#br#[J]. CHINESE JOURNAL OF MEDICINAL GUIDE, 2023, 25(9): 952-956.

参考文献

[1]Xu J，Zhang Y，Jia R，et al. Anti-PD-1 antibody SHR-1210 combined with apatinib for advanced hepatocellular carcinoma，gastric，or esophagogastric junction cancer：an open-label，dose escalation and expansion study[J]. Clin Cancer Res，2019，25(2)：515-523.
[2]Wang LY，Gong S，Gao LP，et al. Apatinib for treating advanced intrahepatic cholangiocarcinoma after failed chemotherapy：a case report and literature review[J].Medicine (Baltimore)，2018，97(49)：e13372.
[3]Wu S，Zhou J，Guo J，et al. Apatinib inhibits tumor growth and angiogenesis in PNET models[J]. Endocr Connect，2019，8(1)：8-19.
[4]Jeon Y，Park EJ，Lim JH，et al. Clinical outcomes of complete cytoreduction with concurrent liver resection followed by hyperthermic intraperitoneal chemotherapy for synchronous peritoneal and liver metastatic colorectal cancer[J].World J Surg Oncol，2019，17(1)：214.
[5]Gibbs P，Heinemann V，Sharma NK，et al. Effect of primary tumor side on survival outcomes in untreated patients with metastatic colorectal cancer when selective internal radiation therapy is added to chemotherapy：combined analysis of two randomized controlled studies[J].Clin Colorectal Cancer，2018，17(4)：e617-e629.
[6]Du X，Chen D，Lin Z，et al. Efficacy of apatinib in advanced hepatocellular carcinoma with lung metastasis： a retrospective， multicenter study[J]. J BUON， 2019， 24(5)：1956-1963.
[7]Xu F， Jin T， Zhu Y， et al. Immune checkpoint therapy in liver cancer[J]. J Exp Clin Cancer Res， 2018， 37(1)：110.
[8]Cao W，Liu J，Wang L，et al. Modeling liver cancer and therapy responsiveness using organoids derived from primary mouse liver tumors[J]. Carcinogenesis，2019，40(1)：145-154.
[9]Marin JJG，Briz O，Herraez E，et al. Molecular bases of the poor response of liver cancer to chemotherapy[J].Clin Res Hepatol Gastroenterol，2018，42(3)：182-192.
[10]Llovet JM，Montal R，Sia D，et al. Molecular therapies and precision medicine for hepatocellular carcinoma[J]. Nat Rev Clin Oncol，2018，15(10)：599-616.
[11]Rawat D，Shrivastava S，Naik RA，et al. An overview of natural plant products in the treatment of hepatocellular carcinoma[J].Anticancer Agents Med Chem，2018，18(13)：1838-1859.
[12]Zhu AX，Finn RS，Edeline J，et al. Pembrolizumab in patients with advanced hepatocellular carcinoma previously treated with sorafenib (KEYNOTE-224)：a non-randomised，open-label phase 2 trial[J]. Lancet Oncol，2018，19(7)：940-952.
[13]Shen Y，Zhang ZB，Wu SD，et al. Research on values of GDF-15 level in the diagnosis of primary liver cancer and evaluation of chemotherapeutic effect[J]. Eur Rev Med Pharmacol Sci， 2018， 22(12)：3749-3754.
[14]李苗，朱映霞，段相会. 卡瑞利珠单抗联合甲磺酸阿帕替尼、替吉奥治疗中晚期原发性肝癌的临床观察[J]. 中国医药指南，2023，21(22)：22-25.
[15]刘阳，卢渊全，孙永臣. 阿帕替尼联合SOX化疗方案在不可切除肝癌患者中的应用[J]. 四川生理科学杂志，2023，45(7)：1264-1266，1281.
[16]陈明，丁恩. 阿帕替尼联合经动脉导管灌注化疗栓塞术治疗原发性肝癌的临床效果及对患者免疫功能的影响[J]. 中国医药，2022，17(6)：871-875.
[17]Huang F， Wang BR， Wang YG. Role of autophagy in tumorigenesis， metastasis， targeted therapy and drug resistance of hepatocellular carcinoma[J].World J Gastroenterol，2018， 24(41)：4643-4651.
[18]Raoul JL， Forner A， Bolondi L， et al. Updated use of TACE for hepatocellular carcinoma treatment： How and when to use it based on clinical evidence[J]. Cancer Treat Rev， 2019， 72：28-36.
[19]Sadeghi S，Bejjani A，Finn RS.Systemic therapy for primary liver tumors： cholangiocarcinoma and hepatocellular carcinoma[J]. Surg Oncol Clin N Am，2019，28(4)：695-715.
[20]薛晨祺，徐春阳，姚煜，等. 替吉奥联合阿帕替尼辅助治疗TACE术后原发性肝癌的临床观察及cfDNA与疗效的相关性[J]. 临床与病理杂志，2022，42(11)：2689-2698.
[21]熊金芹，张帆，王卫星. 阿帕替尼联合替吉奥治疗TACE术后的原发性肝癌的临床研究[J]. 中国医院药学杂志，2019，39(18)：1876-1880.
[22]Ling CQ，Fan J，Lin HS，et al. Clinical practice guidelines for the treatment of primary liver cancer with integrative traditional Chinese and Western medicine[J].J Integr Med，2018， 16(4)：236-248.
[23]Li T， Zhao J， Zhang S， et al. Efficacy and safety of apatinib and transcatheter arterial chemoembolization as second-line therapy for advanced hepatocellular carcinoma： a retrospective cohort study[J]. J Cancer Res Ther， 2023， 19(1)：57-63.

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